1. Field of the Invention
The present invention relates to a platinum(II) complex of N-substituted amino dicarboxylate showing anti-cancer activity, and to a preparation method thereof.
2. Description of the Background Art
Cisplatin, a platinum anti-tumor agent, is one of the most widely used anti-tumor agents in the world. Especially, it has been known that cisplatin shows superior antitumor activities against testicular cancer, ovarian cancer, bladder cancer, etc. However, cisplatin has been restricted in use due to its strong adverse effects for kidney, bone marrow and nervous system (D. Lebwohl, R. Canetta, Eur. J. Cancer, 34, 1522 (1998)).
Accordingly, a great deal of researches for the development of platinum complexes showing superior antitumor activities with lower toxicity have been actively performed worldwide. Especially, in order to improve solubility of the platinum complex in water and to reduce toxicity, dicarboxylate anions have been introduced into the platinum complex. As a result, carboplatin has been developed and presently used in clinic (E. Wong, C. M. Giandomenico, Chem, Rev., 99, 2451 (1999)).
Recently, it has been reported that a platinum complex chelated by amino malonate which is a dicarboxylate having amino groups, shows superior anti-tumor activity (O, Gandolfi, H. C. Apfelbaum, J. Blum, Inorg. Chim. Acta, 135, 27 (1987)). This platinum complex is a (O,O)-chelate form in which the platinum atom is coordinated by two oxygen atoms of the dicarboxylate. However, the (O,O)-chelate form of the platinum complex has a problem because it is chemically unstable and thus, easily converted into a (N,O)-chelate form showing no antitumer activity in aqueous solution by a linkage isomerism as follows (J. D. Roberts, W. J. Schmidt, W. P. Tong, M. P. Hacker, Inorg. Chim. Acta, 153, 123 (1988)): 
Such linkage isomerism takes place more readily in aqueous solution for the platinum complexes of amino dicarboxylates such as glutamate and aspartate, and therefore, it has been known that it is very difficult to synthesize a pure (O,O)-chelated complex having superior antitumer activity (T. G. Appleton, J. R. Hall, D. W. Neale, C. S. M. Thompson, Inorg. Chem., 29, 3985 (1990); and Y.-A. Lee, J. Hong. O.-S. Jung, Y. S. Sohn, Bull. Korean Chem. Soc., 15, 669 (1994)).